Corosolic acid attenuates cardiac fibrosis following myocardial infarction in mice.

ABSTRACT

Corosolic acid (CRA) is a pentacyclic triterpenoid isolated from Lagerstroemia speciosa. The aim of the present study was to determine whether CRA reduces cardiac remodelling following myocardial infarction (MI) and to elucidate the underlying mechanisms. C57BL/6J mice were randomly divided into control (PBS­treated) or CRA­treated groups. After 14 days of pre­treatment, the mice were subjected to either sham surgery or permanent ligation of the left anterior descending artery. Following surgery, all animals were treated with PBS or CRA (10 or 20 mg/kg/day) for 4 weeks. After 4 weeks, echocardiographic, haemodynamic, gravimetric, histological and biochemical analyses were conducted. The results revealed that, upon MI, mice with CRA treatment exhibited decreased mortality rates, improved ventricular function and attenuated cardiac fibrosis compared with those in control mice. Furthermore, CRA treatment resulted in reduced oxidative stress, inflammation and apoptosis, as well as inhibited the transforming growth factor ß1/Smad signalling pathway activation in cardiac tissue. In vitro studies further indicated that inhibition of AMP­activated protein kinase α (AMPKα) reversed the protective effect of CRA. In conclusion, the study revealed that CRA attenuated MI­induced cardiac fibrosis and dysfunction through modulation of inflammation and oxidative stress associated with AMPKα.